The application of quantitative approaches to study biology and medicine is an essential underpinning for the advancement of biomedical research. This proposal requests support for the Molecular Biophysics Training Program (MBTP) at Vanderbilt University, which is now nearing the end of its sixth cycle of NIH funding. The goal of our MBTP is to train students to work at the interface between quantitative molecular approaches and key problems in biology and medicine. The MBTP operates in a unique niche, providing a deeper grounding in the physical sciences for trainees who have a life sciences background, and a more thorough exposure to the life sciences and medicine than is usual for students with a physical sciences, mathematics or engineering background. Although the program draws its training faculty from 7 different departments, it is rooted in an established network of common research and training activities. The number of 74 current students associated with the MBTP is > 2.5 times the number (27) from 15 years ago. Moreover, 14 of the current trainees (19%) are from groups that are underrepresented in science. Together, our trainees, the 25 Training Faculty, the scientific staff, and postdoctoral fellows make for a highly collegial and collaborative community. Beyond a personally designed curriculum, trainees meet along with the entire MBTP community for a minimum of two formal research seminars and one informal gathering each month. The scope of research spans the range of modern molecular biophysics, from understanding the principles of protein folding, to structural characterization of membrane proteins, to defining the action of multi-protein cellular machinery, to investigating the movement of biomolecules into, out of, and within cells. Research projects involve a broad spectrum of physical, biochemical, and computational approaches, including x-ray crystallography, NMR, EPR and fluorescence spectroscopies, small angle scattering, cryo-electron microscopy, cell imaging and molecular/cellular simulations. Many trainees utilize multiple approaches. Trainees join the MBTP in their first year of graduate training after choosing a thesis laboratory, with most supported for two years and some for one year. This grant support specifically covers time needed for additional specialized didactic training and the initiation of thesis research. However, all trainees (and their preceptors) remain active in MBTP program activities throughout the duration of their graduate training. Overall, the MBTP enriches each student's research and training experience and is designed to foster the development of the next generation of independent biomedical scientists.